Altered somatosensory barrel cortex refinement in the developing brain of Mecp2-null mice

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Rett syndrome (RTT) is a neurodevelopmental disorder linked to methyl-CpG binding protein 2 (MeCP2) gene mutations.
• Previous studies suggest monoaminergic system dysfunction in RTT pathogenesis.
• Limited data exist on how monoamine impairment contributes to early RTT symptoms.

Purpose of the Study:

• To investigate the role of MeCP2 deficiency in early neurodevelopment, specifically in the somatosensory barrel cortex.
• To examine the impact of MeCP2 loss on serotonin (5-HT) levels and related gene expression during postnatal development.

Main Methods:

• Utilized a B6.129P2(C)-Mecp2(tm1.1Bird) mouse model (Mecp2-null mice) for RTT research.
• Employed histochemistry to analyze the somatosensory barrel cortex.
• Measured 5-HT levels using high-performance liquid chromatography with electrochemical detection (HPLC/EC).
• Quantified serotonin transporter (SERT) and 5-HT1B receptor mRNA expression in the somatosensory cortex, thalamus, and striatum at postnatal days 10, 20, and 40.

Main Results:

• Mecp2-null mice exhibited significantly smaller barrel fields on postnatal days 10 and 40 compared to wild-type controls.
• Thalamic 5-HT levels were reduced in Mecp2-null mice.
• No significant differences in cortical 5-HT, SERT, or 5-HT1B mRNA were observed at postnatal day 10.

Conclusions:

• The absence of MeCP2 may disrupt the refinement of the barrel cortex during early postnatal development.
• Reduced thalamic 5-HT is implicated as a potential factor contributing to these developmental disturbances in RTT.